Question: A 65-year-old man visited our department during postoperative radiotherapy for an anorectal carcinoma (ARC) with painful penile induration. There were no signs of fever, dysuria, or inguinal lymphadenopathy. On examination, multiple discrete nodules up to 10 mm in diameter were palpable under the prepuce. Three months before the present consultation, the patient underwent abdominoperineal resection for locally advanced ARC. Preoperative radiographic examination could not detect these lesions. Histologic diagnosis of the anorectal lesion revealed a moderately to poorly differentiated adenocarcinoma with a T3 tumor of the positive adventitial margin, resulting in Dukes’ classification B. Laboratory data, including levels of tumor markers, were within the normal range. Serologic tests for syphilis and antibodies of human immunodeficiency virus (HIV) type 1 and type 2 were negative. Magnetic resonance imaging detected multiple penile nodules in (Figure A, T1-weighted, sagittal section, arrows; Figure B, T2-weighted, axial section, an arrow). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. These findings raised a very strong suspicion of penile metastasis (PM). Because PMs usually originate from urogenital malignancies, ARCs are an exceptional source. The differential diagnosis included primary penile tumor, Kaposi sarcoma, tuberculosis, chancre, and chancroid.1Powell B.L. Craig J.B. Muss H.B. Secondary malignancies of the penis and epididymis: a case report and review of the literature.J Clin Oncol. 1985; 3: 110-116Crossref PubMed Scopus (78) Google Scholar The bioptic specimen did indeed confirm this as a metastasis of adenocarcinoma (Figure C, ARC; D, PM). Further investigation showed the same immune profiles having positive staining for cytokeratin 7 (Figure E, ARC; F, PM), but negative for cytokeratin 20. After this diagnosis had been made, the patient underwent palliative chemotherapy, including a molecular-targeted agent. Fortunately, he obtained relief of pain and regained his health with no indication of further metastases 9 months after initial presentation of penile nodules. PMs generally occur in the context of widespread cancers. Despite its abundant blood supply, as well as its proximity to the rectum, the penis is privileged to evade a broad metastatic spectrum of ARCs.2Park J.C. Lee W.H. Kang M.K. et al.Priapism secondary to penile metastasis of rectal cancer.World J Gastroenterol. 2009; 15: 4209-4211Crossref PubMed Scopus (20) Google Scholar The route involving retrograde transportation from the pudendal area into the dorsal penile venous system is currently considered the main pathway for PM (Figure G).3Pernkopf anatomy, volume II. 3rd ed. Urban & Schwarzenberg, Baltimore-Munich1989Google Scholar Clinical presentation of PM includes malignant priapism, painful nodules or ulcerations, urinary retention, dysuria, and hematuria. Because the corpus cavernosum is more likely to be involved than the glans penis or corpus spongiosum, PM in the corpus cavernosum may present malignant priapism as the most frequent symptom.2Park J.C. Lee W.H. Kang M.K. et al.Priapism secondary to penile metastasis of rectal cancer.World J Gastroenterol. 2009; 15: 4209-4211Crossref PubMed Scopus (20) Google Scholar In view of the poor outcomes of all of the reported modalities, total penectomy should be avoided so as to prevent further deterioration of the patient’s quality of life, including the physical and psychological ramifications of penectomy, in what is almost certainly a terminal manifestation of virulent ARCs. PM is rare; however, awareness of this entity is essential for early detection and precise diagnosis, which should be followed by noninvasive treatment to improve quality of life of the patients. Importantly, PM may reflect not locally but systemically aggressive behaviors of advanced cancers with poor prognosis.