The prognostic significance of the peripheral blood absolute lymphocyte count (ALC) has been carefully examined in lymphoid malignancies, but the importance of the baseline ALC in chronic myeloid neoplasms is less clear. In a recent analysis of myelodysplastic syndromes (MDS) associated with deletion of chromosome 5q, we observed that an ALC < 1.2 ×109 cells/L at diagnosis is independently associated with poorer survival. Clinicopathological data from 503 patients with non-del(5q) MDS evaluated at Mayo Clinic between 1996 and 2007 were reviewed to determine the prognostic impact of ALC at diagnosis in non-del(5q) MDS. Patients with MDS and an ALC at diagnosis ≥1.2 × 109 (N = 248) experienced a superior overall survival (OS) compared with patients with an ALC < 1.2 × 109/L (N = 255, median OS of 26.6 months versus 18.5 months, P < 0.001, respectively). ALC at diagnosis was an independent predictor for OS when compared with the International Prognostic Scoring System and the WHO-based Prognostic Scoring System. This study suggests that ALC at diagnosis is a prognostic factor for OS in MDS, and argues in favor of further studies to assess the role of host immunity in MDS clinical outcomes.