Follicular lymphoma is characterized by a highly variable clinical course ranging from early transformation and disease-related mortality to prolonged periods of disease stability or even spontaneous remissions. This clinical heterogeneity is likely explained by differences in the tumor microenvironment, including variable infiltration by monocyte-derived cells. Therefore, we examined the absolute monocyte count obtained from a standard complete blood count with differential at the time of diagnosis as a prognostic factor in a cohort of patients with follicular lymphoma (n = 355) treated at a single institution between 1998 and 2007. We found that the absolute monocyte count at diagnosis is associated with overall survival, independent of the Follicular Lymphoma International Prognostic Index (FLIPI). Furthermore, the absolute monocyte count improved the ability to identify high-risk patients when used in conjunction with the FLIPI. These results further support the central role of non-neoplastic myeloid-lineage cells in follicular lymphoma biology.