Background: Acute basophilic leukemia is a rare subtype of acute myeloid leukemia, as categorized by the 2008 World Health Organization classification of myeloid neoplasms. Acute basophilic leukemia diagnosis requires thorough morphological, cytochemical, immunophenotypic, molecular, and cytogenetic studies and exclusion of other hematological neoplasms associating basophilia. The disease course is defined by histamine driven, occasionally life-threatening respiratory, cardiovascular, cutaneous or digestive complications, as well as primary refractoriness to standard therapy. Clinical presentation: We herein report a case of a 63-year-old asthmatic female patient diagnosed with acute basophilic leukemia, associated with previously unpublished cytogenetic features and FLT-3 ITD mutation, pulmonary leukostasis and spontaneous pulmonary capillary leak syndrome, which worsened immediately following chemotherapy initiation. Respiratory complications were successfully managed, but recrudesced upon emergence of refractory disease and were ultimately fatal. We highlight the likelihood of pulmonary complications induced by basophil degranulation and tumor lysis in hypercellular acute basophilic leukemia and the potential benefit of histamine receptor blockade in this setting.