We have examined tumor cell DNA content as a possible variable in the behavior of early rectal cancer treated by local excision. Flow cytometry assays of tumor cell DNA content were carried out on specimens of archived, paraffin-embedded tissue specimens from 30 patients (11 male and 19 female) whose early rectal cancers were treated by curative local excision more than 60 months previously. The cancers invaded to the muscularis mucosae in 2 patients (1 with aneuploid disease and 1 with diploid disease), into the submucosa in 15 patients (7 with aneuploid disease and 8 with diploid disease), and the muscularis propria in 13 patients (8 with aneuploid disease and 5 with diploid disease). A total of 16 patients had aneuploid disease and 14 had diploid disease. Local recurrence of cancer developed in 12 patients. Of these 12 patients, 10 (83 percent) had aneuploid disease. By contrast, of the 18 patients who remained free of disease, 12 (67 percent) had diploid disease. Seven of the 12 patients with recurrence died. Six of these seven (86 percent) had aneuploid disease. The aggressive clinical behavior of the tumors with aneuploid DNA content was not otherwise predictable by standard histologic features. Aggressive tumor behavior appears to correlate closely with aneuploidy in locally treated rectal cancers, as opposed to a lack of correlation in our patients treated with major resection. The fact that these cancers are being treated by local excision may allow the prognostic impact of DNA content to reflect the natural history of cancer.