Cytogenetic analysis of four well-differentiated malignant epithelial tumors revealed primary clones with only numerical abnormalities. The karyotypes were 49,XX, +5, +5, +7, +7, -17/50,XX, +5, +5, +7, +7, -17, +r in an adenocarcinoma of the lung; 47,XX, +3/47,XX, +5/47,XX, +7 in a squamous cell carcinoma of the epiglottis; 47,XX, +5/48,XX, +5, +10 in a squamous cell carcinoma developing in an ovarian dermoid cyst; and 52,XX, +5, +7, +8, +14, +15, +21 in a seropapillary ovarian adenocarcinoma. Also, in previously published cases exclusively numerical aberrations were much more common in highly differentiated epithelial tumors (22/74) than in moderately to low-differentiated carcinomas (13/281). Our findings and the literature data thus agree with a developmental scheme in which numerical changes, possibly reflecting an early-onset genomic instability in the tumor cells, may precede massive structural anomalies in the gradual malignization of epithelial tumors.