PurposeThe macroscopic diagnosis of tumor invasion through the serosa during surgery is not always distinct in patients with gastric cancer. The prognostic impact of the difference between macroscopic findings and pathological diagnosis of serosal invasion is not fully elucidated and needs to be re-evaluated.Materials and MethodsA total of 370 patients with locally advanced pT2 to pT4a gastric cancer who underwent curative surgery were enrolled in this study. Among them, 155 patients with pT3 were divided into three groups according to the intraoperative macroscopic diagnosis of serosal invasion, as follows: serosa exposure (SE)(-) (no invasion, 72 patients), SE(±) (ambiguous, 47 patients), and SE(+) (definite invasion, 36 patients), and the clinicopathological features, surgical outcomes, and disease-free survival (DFS) were analyzed.ResultsA comparison of the 5-year DFS between pT3_SE(-) and pT2 groups and between pT3_SE(+) and pT4a groups revealed that the differences were not statistically significant. In addition, in a subgroup analysis of pT3 patients, the 5-year DFS was 75.1% in SE(-), 68.5% in SE(±), and 39.4% in SE(+) patients (P<0.05). In a multivariate analysis to evaluate risk factors for tumor recurrence, macroscopic diagnosis (hazard ratio [HR], SE(-) : SE(±) : SE(+)=1 : 1.01 : 2.45, P=0.019) and lymph node metastasis (HR, N0 : N1 : N2 : N3=1 : 1.45 : 2.20 : 9.82, P<0.001) were independent risk factors for recurrence.ConclusionsGross inspection of serosal invasion by the surgeon had a strong impact on tumor recurrence in gastric cancer patients. Consequently, the gross appearance of serosal invasion should be considered as a factor for predicting patients' prognosis.