CA 242, a sialylated carbohydrate epitope situated on the same macromolecule as CA 50 has been proposed as a new tumour marker for pancreatic cancer (PC). The aims of the present study were: (1) to evaluate serum CA 242 versus CA 19-9 in PC patients, and (2) to assess whether these markers can predict tumour spread or patient survival. We studied 59 healthy controls, 27 PC patients, 12 chronic pancreatitis cases, 107 with extra-pancreatic gastrointestinal tumours, 30 with benign jaundice and 24 with benign extra-pancreatic gastrointestinal diseases. Mean CA 242 values were significantly higher in PC than in any other group; CA 19-9 showed a similar pattern. The best diagnostic efficacy (ROC curves analysis) in diagnosing PC was 86% for CA 242 and 84% for CA 19-9, using cut-off values of 60 and 80 U/ml, respectively. In PC, serum levels of both markers were unrelated to tumour spread or size; in PC patients with high levels of CA 242 or CA 19-9 survival was significantly shorter. CA 242 and CA 19-9 were correlated both when considering all the patients together (r = 0.962, p < 0.001) and PC alone (r = 0.880, p < 0.001). Given the very close relationship between CA 242 and CA 19-9, we tested for cross-reactivity between CA 242 antigen and CA 19-9 antibody: CA 242 antigen with CA 19-9 antibody produced a similar curve to CA 242 antigen and its corresponding antibody. In conclusion, CA 242 showed similar diagnostic values to CA 19-9 in assessing PC patients; both seem unrelated to tumour size or spread, but seem to predict survival. Their remarkably similar behaviour is due to cross-reactivity between CA 242 antigen and CA 19-9 antibody, so CA 242 cannot, in our opinion, be considered a new tumour marker for PC.