This chapter explains how normal cells maintain controlled proliferation through antigrowth signals, contact inhibition, and dependence on mitogens. Cancer arises when these controls are lost through cellular transformation, a process marked by altered morphology, loss of contact inhibition, anchorage-independent growth, immortalization, and reduced growth factor dependence. Transformation is driven by oncogene activation and tumor suppressor loss, frequently involving signaling pathways such as RAS and PI3K–AKT. Point mutations, amplifications, translocations, and epigenetic alterations activate oncogenes, while viruses can introduce constitutively active oncogenes, exemplified by v-src of Rous sarcoma virus (RSV). MYC emerges as a central regulator downstream of multiple pathways, driving transcriptional programs that promote virtually all cancer hallmarks. Chromosomal rearrangements such as the BCR-ABL1 fusion in CML or MYC-IGH in Burkitt lymphoma illustrate how genome architecture contributes to oncogenesis. The hallmark framework describes the core capabilities cancer cells acquire, such as sustained proliferation, evasion of growth suppression and cell death, replicative immortality, angiogenesis, invasion, and metastasis, expanded to include genome instability, immune evasion, metabolic rewiring, phenotypic plasticity, epigenetic reprogramming, microbiome influences, and roles of senescent cells. Tumor evolution requires only a few high-impact driver events, particularly when mutations affect broad signaling networks, explaining variability in cancer onset across individuals.