Absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation for multiple myeloma (MM) has been reported to be an independent prognostic factor for clinical outcome. The role of ALC on survival in newly diagnosed untreated MM patients is unknown. Between 1994 and 2002, we analysed retrospectively 537 MM patients of 1835 consecutive MM patients that were neither uniformly treated nor part of a clinical trail, but originally diagnosed and followed at the Mayo Clinic. The primary endpoint was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). The median follow-up was 35.1 months (range: 1-152.5 months). ALC, as a continuous variable, was identified as prognostic factor for OS (Hazard ratio = 0.473, 95% confidence interval = 0.359-0.618, P < 0.0001). MM patients with an ALC >/=1.4 x 10(9)/l experienced superior OS compared with MM patients with an ALC <1.4 x 10(9)/l (65 vs. 26 months, P < 0.0001). Multivariate analysis identified ALC as an independent prognostic factor for OS. This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM.