Palmar-Plantar Erythrodysestasia Syndrome (PPES) or Hand-Foot Syndrome (H&F S) is an underestimated adverse reaction to chemotherapeutic agents, mainly related to 5-Fluorouracil. From March 1991 to February 1992, at the San Giovanni Oncologic Hospital of Torino, we observed 12 out of 163 patients (7.3%) displaying PPES while being treated with 5-FU containing regimens. No correlation with type of neoplastic disease, sex, age and total dose of administered 5FU was observed. Dose reductions or drug suspension achieved PPES reversal. The etiopathogenesis remains unclear. Both an idiosyncratic pattern and cutaneous drug accumulation are suggested.