We examined, with an enzyme-linked immunoadsorbent assay (ELISA) method, the serum of 55 patients with Colon Adenocarcinoma (CA) for the presence of autoantibodies against tropomyosin (TMS), of IgM and IgG isotypes, before and 1 month after surgery. Twenty-six (26) patients with benign surgical diseases (BSD) (hernia or cholelithiasis) and 40 healthy volunteers were used as controls. Preoperatively, 20/55 (36.3%) of CA patients and 2/26 (7.7%) of BSD patients were positive for anti-TMS antibodies, while postoperatively, the positive samples were 22/55 (40%) and 2/26 (7.7%), respectively. The difference between the group of CA patients and the two control groups was statistically significant (p < 0.001). The presence of anti-TMS antibodies has been associated with better outcome of CA patients: 30 CA patients (30/55, 54.5%) had detectable anti-TMS antibodies either preoperatively or postoperatively and 25 CA patients (25/55, 45%) were completely negative in both occasions. In the first group of patients, four (4) recurrences were detected (4/30, 13.3%) while in the second group nine (9) recurrences were found (9/25, 36%). The difference between the two groups was statistically significant (p < 0.01). Anti-tropomyosin antibodies could be used as biological markers of prognosis in colon cancer patients.