We hypothesized that the lack of association between CDK4/6 amplifications, CCND1/2/3 amplifications, and/or CDKN2A/B alterations and outcome after administration of CDK4/6 inhibitors may be due to intratumoral heterogeneity and complexity, resulting in a large proportion of metastatic tumors with cyclin alterations also carrying genomic co-alterations that differ from patient to patient. This evidence concerns the gene CDKN2A and metastatic neoplasm.