A spontaneous T-cell-rich B-cell lymphoma (TCRBCL) occurred as a subcutaneous mass in the buccal region and enlarged submandibular lymph node in a 6-year-old female cynomolgus monkey (Macaca fascicularis). The constituent cells were examined by histology, immunohistochemistry and the double labeled-immunofluorescence method (dl-IF). Further, in situ hybridization (ISH) was employed to detect the gene expression of Epstein Barr virus (EBV). Histologically, the mass was comprised mainly of neoplastic large lymphoid cells and reactive small mononuclear cells. Immunohistochemically, the neoplastic large lymphoid cells were positive for CD20, CD79 alpha, MHC class II, and either IgG, IgM, or IgA. Polyclonal Ig production by the neoplastic large lymphoid cells was demonstrated by dl-IF, although IgG-positive ones predominated in number. On the other hand, most of the small mononuclear cells were positive for CD3 and were regarded as reactive T lymphocytes, while the remaining cells appeared to be histocytes or reactive B-cells. Transcripts of EBV gene were not demonstrated in these neoplastic or reactive cells by ISH. This is the first reported case of spontaneous TCRBCL in the cynomolgus monkey.