Type III procollagen (amino-terminal propeptide of procollagen type III) and type IV collagen are considered to be reliable serum markers for monitoring the progression of liver fibrosis. The peritoneal dissemination of gastric cancer is also characterised by abundant collagen deposition in the peritoneum. The present study was performed to investigate the potential of serum type III procollagen and IV collagen as biomarkers for peritoneal dissemination in gastric cancer. The study population consisted of 117 patients with gastric cancer: 32 patients had peritoneal dissemination which was pathologically diagnosed by laparotomy or laparoscopic examination, while 85 patients (45/40, early/advanced gastric cancer) had no peritoneal dissemination. We measured the serum levels of type III procollagen and type IV collagen in comparison to the commonly accepted tumor markers carcinoembryonic (CEA), carbohydrate antigen (CA)19-9 and CA125. The median type III procollagen levels showed no significant differences between the two groups, whereas the median type IV collagen levels were significantly (201 ng/ml) higher in patients with than in those without peritoneal dissemination (early/advanced gastric cancer, 124/136 ng/ml) (P<0.05). In receiver operating characteristic (ROC) curve analysis, type IV collagen had the largest area under the curve (0.83), followed by CA125 (0.72), CA19-9 (0.64), CEA (0.59) and type III procollagen (0.48). Type IV collagen was an independent marker (P<0.0001, odds ratio 15.7) for predicting peritoneal dissemination along with CA125 (P=0.0086, odds ratio 9.4) based on multivariate logistic regression. In conclusion, serum type IV collagen levels may be significant in the early detection and management of patients with peritoneal dissemination of gastric cancer.