Local and distant tumor spread was evaluated and compared with DNA content analyzed by flow cytometry of eight samples from each of 71 renal cell carcinomas. Twenty-six tumors were homogenously diploid while 45 tumors contained at least one aneuploid tumor sample. Diploid tumors generally respected the surrounding tissues and only three of 26 tumors (12%) had evidence of local tumor invasion. In contrast, 33 of 45 patients (73%) with aneuploid tumors had local invasion (p less than 0.001). Local metastases in lymph nodes and adrenal was found only in patients with aneuploid tumors. However, distant metastases appeared in about the same frequency in patients with diploid and aneuploid tumors (35 and 29%, respectively). Patients with diploid tumors had significantly more often solitary metastases and, most interestingly, the occurrence of lung metastases was a characteristic feature for patients with aneuploid tumors (p less than 0.02). The diploid primary tumors with distant metastases generally were devoid of local invasion while all aneuploid tumors with distant metastases had local invasion and mostly also local metastases. Thus, different characteristics of tumor spread were shown for diploid and aneuploid tumors and the pathways for spread with distant metastases might also differ between these tumors.