The search for pharmacological approaches to neoplastic disease has made some impressive gains started after 1940 when the antileukemic activity of nitrogen mustard was discovered during world war II. It is generally accepted that neoplastic transformation is related to genes alteration or oncogene activation, so the progress in the development of the new drugs for treatment of malignant diseases has been rapid, both in revealing pathobiology of the diseases and discovery of new drugs. In addition attempts have been made to define optimal combinations, treatment strategies and patient support measures. Cancer chemotherapy is now of established value and a highly specialized field. Among the modifications to the family of antitumor compounds, heterocyclic organic compounds have been extensively applied by many groups in order to modify the reactivity profile. Pyrrole, pyrimidine, indole, quinoline and purine are few classes of heterocycles which showed interesting cytotoxicity profiles. The updated material related to these modifications has been rationalized and ordered, in order to offer an overview of the argument.