We developed and tested a new putative analgesic cream, based on the anticonvulsant phenytoin in patients suffering from treatment refractory neuropathic pain. The use of commercial topical analgesics is not widespread due to the facts that capsaicin creams or patches can give rise to side effects, such as burning, and analgesic patches (e.g., lidocaine 5% patches) have complex handling, especially for geriatric patients. Only in a few countries, compounded creams based on tricyclic antidepressants or other (co-)analgesics are available. Such topical analgesic creams, however, are easy to administer and have a low propensity for inducing side effects. We, therefore, developed a new topical cream based on 5% and 10% phenytoin and described three successfully treated patients suffering from neuropathic pain. All patients were refractory to a number of other analgesics. In all patients, phenytoin cream was effective in reducing pain completely, without any side effects, and the tolerability was excellent. The onset of action of the phenytoin creams was within 30 minutes. Phenytoin cream might become a new treatment modality of the treatment of neuropathic pain.