A 15-year-old male individual treated with isotretinoin for acne vulgaris presented with persistent pancytopenia and circulating myeloblasts after discontinuation of the drug. Marrow assessment revealed myelofibrosis (MF) and myeloblasts exhibiting monosomy 7, diagnostic of myelodysplastic syndrome (MDS). Although a popular website seems to associate isotretinoin with MF, no published cases of MF or MDS attributable to this drug were identified. Although we expect that he would eventually have developed MDS and MF, this patient was perhaps identified sooner due to cytopenias accelerated by isotretinoin. This case illustrates that patients exhibiting cytopenias persisting following isotretinoin therapy merit evaluation for underlying hematopoietic disorders.