Abstract Tumor infiltrating mast cells have at least two potential roles in remodeling tumor microenvironment and tumor growth: suppression of immune responses and potentiation of angiogenesis. We have recently shown that accumulation of mast cells in follicular lymphoma (FL) contributes to unfavorable survival after immunochemotherapy. Interestingly, high mast cell content eliminates the positive prognostic value of tumor-associated macrophages (TAMs). Here we investigated whether tumor vascularity, as determined by CD31 immunostaining, is associated with mast cell content and outcome of primary FL patients treated with combination of rituximab (R) and CHOP chemotherapy. We found that increased microvessel density (MVD) correlates positively with the number of tumor infiltrating mast cells (r=0.266, p=0.011). In a cohort of 95 patients, the patients with high MVD (>the lowest tertile) had a worse 4-year progression free survival (PFS) (44% vs 82%, p=0.001). In multivariate analysis with FLIPI, MVD retained its negative predictive value. Additional prognostic impact was especially provided in patients with low FLIPI scores. When MVD related outcome was estimated separately for patients with high and low mast cell contents, the adverse effect of high MVD on the PFS was seen in both subgroups. Taken together, the data demonstrate that MVD is associated with mast cell content and adverse outcome in R-CHOP treated FL patients. In contrast to TAMs, the predictive value of MVD is independent of tumor infiltrating mast cells.