Lancet Oncol 2022; 23: e251–312Published OnlineMay 9, 2022 https://doi.org/10.1016/S1470-2045(21)00720-8 In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in <span class="attribute-to-highlight medbox">cancer</span> incidence and mortality. Without rapid interventions, data estimates show a major increase in <span class="attribute-to-highlight medbox">cancer</span> mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of <span class="attribute-to-highlight medbox">cancer</span> in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing <span class="attribute-to-highlight medbox">cancer</span> crises. Recommended actions begin with the need to develop or update national <span class="attribute-to-highlight medbox">cancer</span> control plans in each country. Plans must include childhood <span class="attribute-to-highlight medbox">cancer</span> plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing <span class="attribute-to-highlight medbox">cancer</span> registries and <span class="attribute-to-highlight medbox">cancer</span> diagnostics for core <span class="attribute-to-highlight medbox">cancer</span> tests.