The last special issue of Cytogenetics and Genome Research on Cancer Genomics was published in 2007. Since then, there have been astonishing developments in the fields of molecular genetics and translational medicine. Clinical and research investigations have shown that the cytogenetic and molecular genomic abnormalities in hematologic and solid tumor malignancies are specific to manifestation of disease development and progression. However, the heterogeneous nature of these genomic alterations has hindered understanding of their significance as the malignant state evolves and of their impact on survival and remission after treatment. The introduction of high-resolution technologies has helped to unravel the complexity of many cancer-associated genomic alterations. Studies like array comparative hybridization (aCGH), single nucleotide polymorphism analyses (SNP), next-generation sequencing (NGS), and gene expression analyses (GEP), have facilitated a more thorough understanding of the pathology of hematologic and solid tumor neoplasms. This issue contains representative articles to further knowledge of the manifestation and progression of cancer. It adds to the ongoing efforts to ultimately create personalized treatments and to eventually eliminate the devastation of malignancy in patients.