A common chronic feature of sickle cell disease is the presence of painful, punched-out leg ulcers. Other cutaneous findings in patients with homozygous sickle cell disease have not been described in the literature. We present a case of a 50-year-old black woman with sickle cell disease who was admitted for acute onset of arm and hip pain. After admission she deteriorated clinically, with multiorgan failure and mental status changes. Examination of the skin revealed erythematous papules and plaques with scaly centers and purpura on the upper trunk. The clinical differential diagnosis was vasculitis versus sepsis. Skin biopsy of two representative lesions was performed. Hematoxylin- and eosin-stained sections showed a superficial perivascular mixed inflammatory infiltrate with numerous eosinophils and extravasated erythrocytes, some of which exhibited bizarre morphology of sickled red blood cells. These findings indicated that the patient's cutaneous lesions, possibly multifactorial in origin, could be a component of her sickle cell crisis. This case is presented as an unusual one in which evaluation of erythrocyte morphology contributed to patient management and to emphasize the importance of examining erythrocyte morphology as a part of the histologic evaluation of stained tissue.