The ultrastructural modes of lymphatic and blood vessel invasions were studied comparatively in hamsters with squamous cell carcinoma (O-1N) that had a high potential for lymph node metastasis. The endothelial injury, which was caused by mechanical stretching with the growth of O-1N, was the initial and characteristic feature common to both vascular invasions. Tumor cell nests penetrating the lymphatic lumen through disrupted endothelial cells still maintained their volume and continuity to the underlying tumor cell nests. In contrast, pronounced microthrombotic and neutrophilic reactions occurred at the site of blood vessel penetration. Within the lymphatic lumen, large clusters of O-1N cells were kept longer in spite of lymphocytic and macrophagic reactions. In blood vessels, clusters of tumor cells that had passed through dense fibrin layers were reduced in size and further disintegrated into smaller pieces by neutrophils. In conclusion, lymphatic invasion is a mechanical process, and smooth and direct invasion of large tumor cell nests into lymphatic vessels is responsible for causing more prompt and frequent lymph node metastasis in O-1N than a hematogenous type.