Histiocytoid Sweet’s syndrome is a recently described histopathologic variant of Sweet’s syndrome. This is the first case report describing histiocytoid variant of Sweet’s syndrome caused by all-trans retinoic acid in a patient with acute promyelocytic leukemia. We present a 30-year-old man with newly diagnosed acute promyelocytic leukemia who received induction chemotherapy containing all-trans retinoic acid and developed fever and painful erythematous cutaneous papules on day 13 of therapy. A diagnosis of histiocytoid Sweet’s syndrome was made. All-trans retinoic acid was considered the culprit drug to induce this event. Treatment with corticosteroids improved the systemic and cutaneous signs. A literature search identified only 17 cases of Sweet’s syndrome during all-trans retinoic acid therapy, but none were of the histiocytoid variant. The presented clinical course resembles previously reported cases of Sweet’s syndrome. This case emphasizes the rare effect of all-trans retinoic acid therapy causing histiocytoid Sweet’s syndrome manifesting as fever and skin papules.