Diffuse large-cell B lymphoma of the pancreas is a rare disease, representing less than 1% of all non-Hodgkin's lymphomas and less than 0.9% of all malignant tumors of the pancreas. About 150 cases of the disease have been observed so far. The tumors are more frequent in the head of the pancreas then in other parts of the organ. They are usually larger (average size of 8 cm) and are non-resectionable. As a rule, exact diagnosis is based on the histology and the immunohistology of the specimen taken during open surgery performed for general diagnosis of the pancreatic tumor. Very rarely can a very reliable and experienced cytopathologist establish a proper diagnosis based on material obtained from a fine needle biopsy. The disease usually responds positively to immunochemotherapy according to protocol R-CHOP. Occasionally, additional radiotherapy may be required. We present two women, 66 and 49 years old, in whom a diagnosis of large-cell B lymphoma of the pancreas was established, based on the histology and the immunohistochemistry of a specimen taken during open surgery performed in order to remove pancreatic tumors, which turned out to be non-resectionable. After immunochemotherapy, the symptoms disappeared and the tumors shrank, in one patient after additional radiotherapy. The authors would like to point out the importance of a proper histological diagnosis, which permitted the application of immunochemotherapy alone or together with additional radiotherapy with at least temporarily favorable results.