To the Editor: Verrucous carcinoma (VC) or carcinoma cuniculatum is a squamous cell carcinoma of low malignant potential, most commonly affecting the foot and leg.1Kao G.F. Graham J.H. Helwig E.B. Carcinoma cuniculatum (verrucous carcinoma of the skin): a clinicopathologic study of 46 cases with ultrastructural observations.Cancer. 1982; 49: 2395-2403Crossref PubMed Scopus (125) Google Scholar Treatment of VC is challenging with multiple medical and surgical therapies often attempted with limited success. We report 2 cases of VC of the foot treated with imiquimod (Aldara) for more than 1 year. This treatment was successful in one case, but did not slow the growth of the verrucous tissue in a second. A 70-year-old man presented with a 2-month history of an intractable ulcer adjacent to his right medial malleolus and on the plantar surface of the heel with a 22 cm × 15 cm malodorous ulceration surrounded by verrucous plaques extending into the medial and lateral surfaces of the proximal right foot (Fig 1, A). Histology revealed superficial epidermal necrosis with marked down-growth of well-differentiated squamous epithelium displaying a glassy, eosinophilic cytoplasm. The deep aspect of the tumor had a bulbous, pushing border consistent with the diagnosis of VC. Imiquimod 5% cream was started once daily applied under occlusion. The ulceration slowly healed over 4 months and the verrucous plaques decreased in size to 3-cm plaques on lateral and medial proximal sides of the foot. After 10 months of therapy, these areas had clinically resolved (Fig 1, B). The patient continues using daily imiquimod without clinical recurrence. A 38-year-old woman presented with a 2 cm × 4 cm exophitic, verrucous mass on her right medial heel (Fig 2). Multiple biopsy specimens confirmed the diagnosis of VC. Treatment consisted of biweekly interferon alfa injections for 33 months and daily imiquimod for 30 months. These therapies were ineffective and have been discontinued. Multiple excisions were performed, each followed by recurrence of the lesion. She continues to be treated with surgical excision. The cause of VC is still unclear but is linked to chronic inflammation/ulceration, earlier injury to the effected area, and scars. Human papillomavirus may be a potential cause. Kao et al1Kao G.F. Graham J.H. Helwig E.B. Carcinoma cuniculatum (verrucous carcinoma of the skin): a clinicopathologic study of 46 cases with ultrastructural observations.Cancer. 1982; 49: 2395-2403Crossref PubMed Scopus (125) Google Scholar failed to find viral particles when examining 14 specimens of VC using immunoperoxidase and electron microscopy without evidence of virus in 1982. Subsequently, human papillomavirus DNA was identified in VC specimens, including types 6b, 11, 16, and 18.2Garven T.C. Thelmo W.L. Victor J. Pertschuk L. Verrucous carcinoma of the leg positive for human papillomavirus DNA 11 and 18: a case report.Hum Pathol. 1991; 22: 1170-1173Abstract Full Text PDF PubMed Scopus (31) Google Scholar, 3Schell B.J. Rosen T. Rady P. Arany I. Tschen J.A. Mack M.F. et al.Verrucous carcinoma of the foot associated with human papillomavirus type 16.J Am Acad Dermatol. 2001; 45: 49-55Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Viral typing was not performed on our two patients. Imiquimod 5% cream, a toll-like receptor 7 agonist, has shown success in the treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma and anecdotal success in invasive squamous cell carcinoma and perianal VC.4Hengge U.R. Ruzicka T. Topical immunomodulation in dermatology: potential of toll-like receptor agonists.Dermatol Surg. 2004; 30: 1101-1112Crossref PubMed Scopus (63) Google Scholar, 5Heinzerling L.M. Kempf W. Kamarashev J. Hafner J. Nestle F.O. Treatment of verrucous carcinoma with imiquimod and CO2 laser ablation.Dermatology. 2003; 207: 119-122Crossref PubMed Scopus (42) Google Scholar Although the exact mechanism of imiquimod is not known, its effects are thought to be a result of augmentation of immune response through induction of interferon alfa.4Hengge U.R. Ruzicka T. Topical immunomodulation in dermatology: potential of toll-like receptor agonists.Dermatol Surg. 2004; 30: 1101-1112Crossref PubMed Scopus (63) Google Scholar Imiquimod has been used been used in conjunction with carbon-dioxide laser for perianal VC,5Heinzerling L.M. Kempf W. Kamarashev J. Hafner J. Nestle F.O. Treatment of verrucous carcinoma with imiquimod and CO2 laser ablation.Dermatology. 2003; 207: 119-122Crossref PubMed Scopus (42) Google Scholar but there is limited experience with using imiquimod for VC otherwise. Our results suggest that imiquimod may be useful in treatment of some cases of VC or as an adjuvant for shrinking the VC before other more definitive surgical therapies. With the response of one patient, further study may be warranted to further delineate the therapeutic usefulness of imiquimod in VC.