We attempted to establish an in vivo experimental model of metastasis of oral caner. The HSC-3 cell line, originating from human oral squamous cell carcinoma, was transplanted into nude mice, and metastases to the lymph node and the lung were investigated using genetic analysis. The HSC-3 cells, transplanted subcutaneously into the lateral back of nude mice, and punctured repeatedly after cyst formation, could metastasize to the lymph node and the lung. Genetic analysis using human beta-globin gene demonstrated that the frequency of metastasis to the lymph node and the lung at 12 weeks after the transplantation was 45% and 40%, respectively. Mutant allele-specific amplification of p53 gene could also detect micrometastasis with almost equal sensitivity of polymerase chain reaction with beta-globin gene. Subcutaneous transplantation is easy with excellent reproducibility compared with intravenous or orthotopic transplantation, and we think that this experimental model can be one of standard models of cancer metastasis.