There is paucity of data regarding the diagnostic yield and safety of skin biopsies in patients with acute myeloid leukemia (AML), though skin eruptions are common in these patients. We evaluated 216 patients treated in our hemato-oncology unit at a tertiary medical center between 2007 and 2018 and identified 35 patients who underwent 37 skin biopsies. The majority of biopsies were performed during induction treatment for AML (n = 26, 70%), whereas the remainder of biopsies were done prior to induction initiation (n = 8, 22%) or during consolidation chemotherapy (n = 3, 8%). Pathology findings were inconclusive in 13 cases (35%), while diagnostic biopsies were positive for drug eruptions (24%), leukemia cutis (16%), infections (11%), reactive processes (8%) and Sweet syndrome (5.5%). In almost half of cases (16/37) tissue cultures were performed. Of those, only a quarter (4/16) were positive. Histopathology and tissue culture results altered immediate patient care in 3 cases (8%), yet information obtained from biopsies had potential to affect long term patient care in 8 additional cases (21.6%). Although most skin biopsies were performed while patients had severe thrombocytopenia and neutropenia, only one patient had a complication due to the biopsy (fever and local bleeding). With the limitation of a retrospective analysis, our study suggests that skin biopsies in patients treated for AML are relatively safe. Although biopsy results infrequently alter immediate patient management, long term effect on patient care expand the potential diagnostic yield of skin biopsies.