Among 4,780 consecutive adult acute lymphoblastic/myeloblastic leukemia patients, we identified 117 (2.4%) patients with mixed-phenotype acute leukemia fulfilling WHO 2008 criteria; these were classified as: Blymphoid+ myeloid (n= 64), T-lymphoid+ myeloid (n= 38), B+ T-lymphoid (n= 14) and trilineage (n= 1). Of 92 patients karyotyped, 59 were abnormal and were classified as: complex (22 of 92), t (9; 22)(q34; q11)(14 of 92), monosomy 7 (7 of 92), polysomy 21 (7 of 92), t (v; 11q23)(4 of 92), t (10; 11)(p15; q21)(3 of 92), while STIL-TAL1 fusion was detected in one (T+ My) patient. After investigating common acute leukemia-related mutations in 17 genes, 12 of 31 (39%) patients were found to have at least one mutation, classified with: IKZF1 deletion (4 of 31), and EZH2 (3 of 31), ASXL1 (3 of 31), ETV6 (2 of 31), NOTCH1 (1 of 31), and TET2 (1 of 31) mutations. Array-CGH revealed genomic deletions of CDKN2A (4 of 12), IKZF1 (3 of 12), MEF2C (2 of 12), BTG1 (2 of 12), together with BCOR, EBF1, K-RAS, LEF1, MBNL1, PBX3, and RUNX1 (one of 12 each). Our results indicate that mixed-phenotype acute leukemia is a complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and molecular genetic features.