Cancer is one of the most common diseases worldwide, and its treatment is associated with many challenges such as drug and radioresistance and formation of metastases. These difficulties are due to tumor heterogeneity, which has many causes. One may be the cell fusion, a process that is relevant to both physiological (e.g., wound healing) and pathophysiological (cancer and viral infection) processes. This literature review aimed to summarize the existing data on the hybrid/atypical forms of circulating cancer cells and their role in tumor progression. For that, the bioinformatics search in universal databases, such as PubMed, NCBI, and Google Scholar was conducted by using the keywords “hybrid cancer cells”, “cancer cell fusion”, etc. In this review the latest information related to the hybrid tumor cells, theories of their genesis, characteristics of different variants with data from our own researches are presented. Many aspects of the hybrid cell research are still in their infancy. However, with the level of knowledge already accumulated, circulating hybrids such as CAML and CHC could be considered as promising biomarkers of cancerous tumors, and even more as a new approach to cancer treatment.