We review the medical literature for the clinical characteristics of patients developing multiple primary neoplasms (MPN). Also, preliminary results of our study at Memorial Sloan Kettering Cancer Center are reported. Although there have been very few specific reports on this topic, it was possible to find some data, suggesting a worse prognosis for patients with MPN. Several factors may be responsible for this, and further studies are in progress. Meanwhile, it is of great importance to decrease the incidence of cancer by prevention, such as reducing smoking and alcohol consumption. This may reduce the incidence of first primary neoplasms and MPN. Optimal treatment for the first primary neoplasm should be given, but the possible risk of MPN should be taken into consideration, and, if there are two alternatives for the treatment of the first tumor, the one that is less carcinogenic and that will allow appropriate therapy for a second primary neoplasm (MPN2) should be chosen. On follow-up of cancer patients, a low threshold of suspicion for a second primary neoplasm is recommended to detect them early for possible curative treatment. Because of the poor prognosis, more aggressive treatment regimens for MPN are warranted.