Recent whole-genome sequencing (WGS) studies have demonstrated that tumors typically comprise a founding clone and multiple subclones (i.e., clonal heterogeneity is common). The possible combination of mutations in each tumor clone is enormous, making each tumor genetically unique. Clonal heterogeneity likely has a role in cancer progression, relapse, metastasis, and chemoresistance due to functional differences in genetically unique subclones. In current clinical practice, gene mutations are only classified as being present or absent, ignoring the clonal complexity of cancers. In this review, we address how tumor clonality is measured using next-generation sequencing (NGS) data, highlight that clonal heterogeneity is common across multiple tumor types, and discuss the potential clinical implications of tumor clonal heterogeneity.