Background: Cancer develops as a result of somatic mutations and evolutionary processes with a Darwinian character. Tumors evolve by dynamic clonal expansion and selection to form genetically diverse cell subpopulations adapted to different tumor microenvironmental conditions. Within cancer cells, the genome is shaped by various selective pressures. Cancer evolution often follows a branched trajectory with divergent subclones evolving simultaneously. Clonal diversity within the same tumor results in genetic, epigenetic and phenotypic variability in tumor mass, which represents a major obstacle for the development of efficient diagnostics and personalized treatment. Advances in sequencing techniques have enabled a better understanding of the growth, progression and response to cancer treatment in heterogeneous cancers. Concurrently, understanding the mechanisms involved and monitoring changes in cancer clones during disease progression may improve the efficiency of cancer therapy. Aim: In this review, we summarize available data on intratumor heterogeneity. We show how intratumor heterogeneity, arising from clonal diversity, manifests itself at various levels, including at the genetic, epigenetic, and protein levels. We describe how phylogenetics, a powerful systems biology approach, can help trace clonal evolution during cancer progression and metastasis formation. We also highlight the main problems caused by intratumor heterogeneity, which hinders the development of novel diagnostics and therapies.