5-fluorouracil (5-FU) is widely used for treatment of malignant and premalignant skin cancers; however, its use in other common cutaneous conditions has been less widely reported. We investigated the off-label uses of 5-FU beyond malignant and premalignant skin disease. We conducted a literature review searching multiple databases to evaluate the evidence for the off-label uses of 5-FU. The level of evidence was evaluated and selected accordingly listing the studies with the highest level of evidence first using the Oxford Centre of Evidence-Based Medicine 2011 guidance. We found underlying evidence to support the use of 5-FU for a wide range of noncancerous cutaneous indications including scarring (keloid, hypertrophic), pigmentary disorders (vitiligo, idiopathic guttate hypomelanosis), cutaneous infections (viral warts, molluscum contagiosum), inflammatory dermatoses (Darier's disease, Hailey-Hailey disease and sarcoidosis), and cosmetic indications (photoaging, treatment of filler nodules and granulomas). In selected patients, 5-FU can be as effective as more established treatments, with fewer side-effects.
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