The search for the cause of cancer has led to five successive theories involving viruses, oncogenes, tumor suppressor genes, somatic mutation cascade and inflammation. The latter, without discarding the former theories, is now the prevailing paradigm recognizing that neoplastic cells require participation of the microenvironment for tumor progression. Inflammatory reactions are dependent on an overabundance of immune responses which are both in favor and against tumor development. This homeostatic immunological behavior has led to the concept of tumor immunoediting in an attempt to elucidate why tumors grow. This review is a non-exhaustive description of the different experimental highlights which have led to our present knowledge of cancer. During its 47 years of existence, our laboratory has contributed extensively to the experimental development of onco-immunology, so that our results are described within the background of international discoveries. As for cancer therapy, the many attempts made, both at the experimental and clinical levels, have been mainly frustrating and yet, as oncologists, we are always ready to try again.