• We assessed the value of 41 skin biopsy specimens obtained from 32 immunocompromised patients with fever and neutropenia. Fifty-six percent (23/41) of these biopsy specimens resulted in a specific diagnosis. These diagnoses included infection in 12 cases, graft-vs-host disease in nine, leukemic infiltrate in one, and drug reaction in one. The remaining 18 biopsy specimens showed either nonspecific changes or normal tissue. The infectious agents identified included Aspergillus in nine patients, Candida in three patients, and Staphylococcus aureus in one patient. As a result of the biopsy findings, therapy was altered in 49% (20/41) of the cases. The most frequent therapeutic change was initiation of amphotericin B for a demonstrated fungal infection. We found skin biopsies to be a valuable diagnostic tool in the assessment of the febrile, neutropenic, immunocompromised patient with skin lesions.