Amplification and overexpression of the c-myc gene and/or the HER2/neu gene are common events in many human breast cancers. Studying the effects of increasing c-myc expression in breast cancer cell lines, we found that the anchorage-dependent growth rate of cells overexpressing HER2/neu is not affected by increased c-myc expression, whereas enhanced expression of c-myc in cells that do not overexpress HER2/neu can slow that growth rate. Increased c-myc expression did not affect anchorage-independent growth in soft agarose in any of the cells, and it slowed the anchorage-dependent growth of only those cells that do not overexpress HER2/neu, suggesting that HER2/neu overexpression may counteract the anchorage-dependent growth inhibition mediated by c-myc.