Published data on flow cytometry (FCM) in diagnosing myelodysplastic syndromes (MDS) varies greatly in analytic methods and interpretational approaches. We tested the diagnostic utility of the pattern recognition approach by a retrospective review of 180 MDS, 31 myelodysplastic/myeloproliferative disease (MDS/MPD), 37 non-MDS cytopenia and 20 myeloproliferative disease (MPD) cases. Cases were placed into "positive", "intermediate", and "negative" FCM categories based upon the antigenic aberrations observed on myelomonocytic cells. By exclusion or inclusion of the intermediate category as indicative of MDS or MDS/MPD, the overall sensitivity and specificity were 84% and 97% or 98% and 78%, respectively. The overall abnormalities detected by FCM correlated with the severity of morphological dysplasia and clonal cytogenetic abnormalities. MPD also demonstrated immunophenotypic aberrancy. Based on a global evaluation of myelomonocytic abnormalities, and recognition of diagnostic pitfalls and caveats, the pattern recognition approach of FCM is sensitive and reliable in diagnosing MDS and related myeloid diseases.