Four patients with colorectal cancer treated with tegafur (a fluoropyrimidine structurally similar to 5-fluorouracil) noted a macular, spotted hyperpigmentation limited to the palms, soles, nails, and glans penis. Histopathologic examination disclosed epidermal basal hyperpigmentation with a lentiginous pattern. Mucocutaneous lesions resolved spontaneously two months after treatment was discontinued. This peculiar phenomenon seems to represent a previously unreported side effect of this cytotoxic drug.