Medical records of all patients who were diagnosed with a malignancy and who underwent a skin biopsy were reviewed to determine the clinical utility of skin biopsies in this population. Skill biopsies resulted in a change or refinement of the prebiopsy diagnosis in 44% of patients undergoing an initial evaluation for a malignancy, 57% of patients on therapy, and 17% of patients off therapy. Skin biopsies led to a change in therapy in 26%, 34%, and 17% of each respective group. Overall, the skin biopsy changed or refined the prebiopsy diagnosis in 45% of cases and altered therapy in 38%. Skin biopsy is a clinically useful tool in pediatric oncology patients for the evaluation of cutaneous findings that elude diagnosis by visual inspection.