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Venetoclax is an approved treatment for relapsed/refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). We report a unique case of venetoclax monotherapy used for front-line induction and as a bridge to allogeneic hematopoietic stem cell transplantation (HCT). Venetoclax therapy resulted in rapid complete resolution of skin lesions, however, treatment interruption due to neutropenia led to brisk cancer recurrence. Fortunately, the patient responded to re-challenge and was able to undergo HCT. Venetoclax is active in the first-line treatment setting for BPDCN, however its effect on blood counts and durability of response should be further studied.