Desmoid tumor is a rare fibroblastic proliferation with a variable and often unpredictable clinical course that arises in the deep soft tissues and is characterized by infiltrative growth with tendency to local recurrence but not to metastasize. A 49-year-old man was referred for a second opinion regarding a pancreatic mass. With a personal neoplastic background of two different tumors, we considered as a high probability of being metastatic of his previous colorectal or renal cancers, in a peritoneal implant. Due to the unclear origin and nature of the mass, we opted for requesting a computed tomography (CT)-guided core needle biopsy that could eventually lead to a surgical and/or chemotherapy treatment. So far, this is the first case of pancreatic desmoid fibromatosis with splenic vein invasion diagnosed by CT scan-guided core needle biopsy. Surgery should be performed by an experienced surgeon as first-line therapy, provided expected surgical morbidity is limited.