Background Complementary and alternative medicine, including homeopathy, is widely used to improve well-being among cancer patients and reduce adverse effects of conventional treatment. In contrast, there are few studies on the use of homeopathic medicines to treat the disease itself. Yet, evidence of possible effectiveness of homeopathic high dilutions in experimental cancer models has been published during the past 20 years. Aim The aim of the study was to perform a systematic review of fundamental research studies on homeopathic high dilutions in cancer. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, we conducted a literature search in the database PubMed for original publications, from 2000 to 2018 and in English, on in vitro and in vivo experimental cancer models testing homeopathic high dilutions. Results Twenty-three articles met the inclusion criteria—14 in vitro, eight in vivo, and one in vitro plus in vivo experimental models. Most studies were from India. Research prominently focused on cytotoxic effects involving apoptotic mechanisms. Intrinsic aspects of homeopathy should be considered in experimental designs to emphasize the specificity of such effects. Conclusion Fundamental research of homeopathy in cancer is still at an early stage and has mainly been performed by a few groups of investigators. The results point to an interference of well-selected homeopathic medicines with cell cycle and apoptotic mechanisms in cancer cells. However, these findings still need independent reproduction.