The prognosis of prostate cancer is mainly determined by the presence or absence of metastases. Nevertheless, the metastatic pathways in prostate cancer are not entirely understood. Among 19,316 routine autopsies performed from 1967 to 1995 on men older than 40 years of age, the reports from those 1,589 (8.2%) with prostate cancer were analyzed. Hematogeneous metastases were present in 35% of 1,589 patients with prostate cancer, with most frequent involvement being bone (90%), lung (46%), liver (25%), pleura (21%), and adrenals (13%). Several lines of evidence suggested the existence of a backward metastatic pathway through veins from the prostate to the spine in addition to classical hematogeneous tumor spread via the vena cava. First, there was an inverse relationship between spine and lung metastases, suggesting that metastasis to the spine is independent of lung metastasis. Second, the maximum frequency of spine involvement occurred in smaller tumors (4 to 6 cm) as compared with the maximum spread to lung (6 to 8 cm) and liver (>8 cm), suggesting that spine metastases precede lung and liver metastases in many prostate cancers. Third, there was a gradual decrease in spine involvement from the lumbar to the cervical level (97% v 38%), which is consistent with a subsequent upward metastatic spread along spinal veins after initial lumbar metastasis. The results of this study show that bone, lung, and liver are the most frequent sites of distant prostate cancer metastases. Besides the cava-type of metastasis through lung passage, there are strong arguments for the existence and clinical significance of a backward venous spread to the spine, which is likely to occur early in the metastatic process.