A recent report indicates that patients with squamous cell carcinoma of the anal canal (SCCAC) and intraepithelial lymphocytes have a poor prognosis. Against that background, histological sections from 277 consecutive SCCACs were reviewed searching for cases with massive tumor-infiltrating lymphocytes (TILs; >/= 50 lymphocytes /100 tumor cells). Of the 277 SCCACs, 8 (3%) had massive TILs. These 8 patients (all females) had both more advanced clinical stage than the remaining 269 control SCCAC patients. Follow-up studies revealed that the 8 patients with SCCACs having massive TILs had a much better 15 years survival rate than control SCCAC patients. It is concluded that despite SCCAC patients with massive TILs had a more advanced clinical stage than SCCAC controls, SCCAC with massive TILs patients had a longer survival rate (with no deaths after 5 years) than control cases. The search via proteomic methodology for the lymphocyte-attracting tumor protein might bring forward a novel co-adjuvant therapy, capable to increase prolonged survival time in patients having SCCAC without massive TILs.