Perineural invasion (PNI) in rectal cancer was studied, prospectively. One-hundred patients (20%) were identified as having tumors with PNI. The incidence of PNI was significantly increased in tumors with moderate or marked venous invasion (30%, 64%), with moderate or marked lymphatic permeation (37%, 72%), with liver metastasis (50%) and with peritoneal dissemination (64%). In cases of curative surgery, the incidence of PNI was significantly increased in MAC stage C2m+g or C3 (28%, 35%). There was no significant difference in the recurrence or survival rates between the patients with PNI and without PNI in MAC stage B2m+g. However, there was a significant increase in local recurrence in the patients with both PNI and lymph node metastasis (p less than 0.05). Also, the patients with PNI in MAC stage C2m+g had a significantly lower 8-year survival rate (29.1%, p less than 0.001). Multivariate analysis using Cox regression models demonstrated that PNI was an independent prognostic factor for survival.