Induction of apoptosis by the tumor suppressor p53 is known to protect from Myc‐driven lymphomagenesis. The p53 family member p73 is also a proapoptotic protein, which is activated in response to oncogenes like Myc. Here, we have investigated whether p73 provides a similar protection from Myc‐driven lymphomas as p53. Confirming previous studies, the inactivation of a single p53 allele (p53^+/−) strongly reduced the median survival of Eμ‐Myc transgenic mice from 103 to 39 days and was invariably associated with a loss of the wild‐type p53 allele. In contrast, mutational inactivation of a p73 allele (p73^+/−) reduced the median survival by only 12 days. Lymphomas that developed in the p73^+/− background showed no loss of heterozygosity (LOH). Furthermore, gene expression profiling of p73^+/+, p73^+/− and p73^−/− lymphomas indicated that p73^+/− lymphomas retained p73 transcriptional activity. Subtle gene expression differences between p73^+/+ and p73^+/− lymphomas, however, suggest a haploinsufficient phenotype on some p73 target genes. This might help to explain why p73^+/− animals succumbed to disease slightly earlier than their p73^+/+ littermates (log‐rank test p < 0.0395) and why p73 often shows monoallelic inactivation in human lymphomas. Together these data demonstrate that in Myc‐driven lymphomagenesis p73 has weak tumor suppressor activity compared with p53. © 2008 Wiley‐Liss, Inc.