A method was developed for obtaining direct chromosome preparations from SENCAR mouse skin tumors induced by chemical carcinogenesis protocols. Papillomas and squamous cell carcinomas were mechanically dispersed immediately after resection and were placed in a modified Hanks' solution with collagenase, trypsin, hyaluronidase, bovine albumin, and Colcemid. Total exposure to Colcemid did not exceed 1 hr. Metaphases were obtained in 100% of the analyzed specimens, allowing chromosome counting screening for double minutes and, in 50% of the cases, useful G-banded slides. The technique described has produced, for this type of tumor, a higher number of successful G-banded preparations than other previously reported methods for solid tumors. This procedure may be applicable for the study of human solid tumors that are histologically similar to our murine model, such as squamous cell carcinoma of cervix or lung.