Expression of the c-myc gene is often elevated in human colorectal tumors, but reported amplification of the locus is rare. Here we demonstrate that modest amplification of c-myc is frequently found in aggressive subtypes of colorectal cancer. Careful quantitation of c-myc copy number has shown amplification in 53.8% (7/13) mucinous tumors, 42.3% (3/7) poorly differentiated tumors and a single poorly differentiated APUD tumor. This contrasts with amplification in 6.9% (2/29) moderately to well differentiated tumors, a value which is in agreement with that in previously published reports. Such changes in gene copy number may represent an important aspect of the genomic alterations which accumulate during the development of colorectal tumors.