Nematodes, such as Caenorhabditis elegans, have been instrumental to the study of cancer. Recently, their significance as powerful cancer biodiagnostic tools has emerged, but also for mechanism analysis and drug discovery. It is expected that nematode-applied technology will facilitate research and development on the human tumor microenvironment. In the history of cancer research, which has been spurred by numerous discoveries since the last century, nematodes have been important model organisms for the discovery of cancer microenvironment. First, microRNAs (miRNAs), which are noncoding small RNAs that exert various functions to control cell differentiation, were first discovered in C. elegans and have been actively incorporated into cancer research, especially in the study of cancer genome defects. Second, the excellent sense of smell of nematodes has been applied to the diagnosis of diseases, especially refractory tumors, such as human pancreatic cancer, by sensing complex volatile compounds derived from heterogeneous cancer microenvironment, which are difficult to analyze using ordinary analytical methods. Third, a nematode model system can help evaluate invadosomes, the phenomenon of cell invasion by direct observation, which has provided a new direction for cancer research by contributing to the elucidation of complex cell–cell communications. In this cutting-edge review, we highlight milestones in cancer research history and, from a unique viewpoint, focus on recent information on the contributions of nematodes in cancer research towards precision medicine in humans.