Association between certain surface markers and acute myelogenous leukemia (AML) with t(8;21) has been described. The specificity and the predictive values of these markers have never been assessed. In this study, we aimed, to explore whether a specific pattern could predict for this translocation. Of 405 consecutive AML, 18 (4.4%) had the t(8;21). Patients with this cytogenetic abnormality showed higher frequency of CD34 (P = 0.003), HLA-DR (P = 0.03), Tdt (P = 0.02), CD19 (P < 0.0001), and CD56 (P < 0.0001) and lower CD33 (P = 0.0001). Taken singly, the sensitivity of these markers for AML with t(8;21) ranged between 39 and 100% with CD34+ having the highest and CD33- having the lowest and the positive predictive values (PPV) ranged between 5 and 21% with CD19+ having the highest and HLA-DR+ having the lowest. When combinations of different markers were analyzed by multivariate analysis, the pattern CD34+/HLA-DR+/MPO+ was found to have the highest sensitivity (100%) with a PPV of 14% and the pattern CD34+/CD19+/CD56+ had the highest PPV (100%) with a sensitivity of 67%. We conclude that AML with t(8;21) is better identified by a combination of markers than by a single antigen pattern, the absence of CD34+, HLA-DR+ or MPO+ would preclude and the expression of the pattern CD34+/CD19+/CD56+ is highly predictive and could serve as a screening criteria for the t(8;21).