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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by bone marrow expansion and the proliferation of one or more myeloid cell lineages, predominantly driven by the expression of the constitutively active fusion product tyrosine kinase BCR:ABL1. Rarely, CML patients directly develop a blast crisis (BC), mostly of myeloid origin. CML at blast crisis with a T-cell phenotype at diagnosis, without any prior history of CML, is extremely rare. Herein, we describe one rare CML case, in a young man showing an unusual and early T-lymphoid blastic crisis at diagnosis, as the first onset of a previously unknown CML. The multidisciplinary collaboration between laboratorians and clinicians for the diagnosis and management of this atypical case was crucial in outlining both a targeted pharmacological treatment and a successful hematopoietic stem cell transplantation.