We studied whether DAP-kinase hypermethylation plays a role as a prognostic marker in patients with follicular lymphoma (FL). We found that DAP-kinase was frequently hypermethylated in bone marrow (BM) samples of 52 FL patients at diagnosis (71%) and identified patients with worse progression-free survival (p=0.06). In particular, patients with histologically proven BM infiltration and DAP-kinase hypermethylation had a poorer outcome (p=0.037). In a total of 170 BM samples obtained at diagnosis or during follow-up, DAP-kinase hypermethylation and the bcl2/IgH rearrangement gave concordant results in 67% of samples (48% both positive, 19% both negative). Both mrakers were independent predictors of the disease status (p<0.001).