Capecitabine is an orally active fluoropyrimidine that has been approved for first-line treatment of metastatic colorectal cancer when fluoropyrimidines alone are indicated. One of the toxicities described in the literature associated with capecitabine is palmar-plantar erythrodysesthesia. Based on a careful review of the literature, no reported cases of erythema, ulceration, and swelling that involves the penis and scrotum have been described in association with capecitabine. The following 2 cases illustrate palmar-plantar erythrodysesthesia with scrotal and penile involvement secondary to capecitabine.