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The diagnosis of hematological malignancies depends on laboratory analysis and often requires multiple experimental methods to judge, otherwise misdiagnosis is apt to happen. Lymph node biopsy immunohistochemistry (IHC) for T-lymphoblastic lymphoma (T-LBL) requires the establishment of antibody set screening. For identifying T-LBL and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) by lymph node biopsy and IHC, WHO has not yet proposed a better IHC antibody combination.Here we reported 1 case with tortuous diagnosis experience. Initially, a 51-year-old man was diagnosed as T-LBL by lymph node biopsy, but in another hospital acute myeloid leukemia (AML) was confirmed by bone marrow puncture. Finally, it was diagnosed as mixed phenotype acute leukemia (MPAL) through our comprehensive evaluation including bone marrow cell morphology, cytochemical staining and flow cytometry analysis. Importantly, the experience about differential diagnosis and our appreciation among the T-LBL, ETP-ALL and MPAL was discussed to enlighten readers.The patient was diagnosed with mixed phenotype acute leukemia (T+My)-NOS.The patient received 1 cycle of VDCLP scheme treatment firstly. The effect of chemotherapy is satisfactory, and then he received continuous treatment and was currently in good condition.This patient is alive at present. The follow-up period has been 1 year.For the diagnosis of T-LBL, the molecular markers of the myeloid and lymphoid tissues need to be included, such as CD117, CD33, Lys and MPO. The bone marrow puncture also needs to be conducted to distinguish T-LBL and T-ALL. Secondly, to identify ETP-ALL and MPAL, bone marrow cell morphology, cytochemical staining as well as flow cytometric analysis were needed to make a clear diagnosis. It is recommended that at least CD8, CD1a, Lys and MPO should be included in the panel to identify ETP-ALL.