A new nude-mouse metastasizing orthotopic transplant model of human adenocarcinoma of the lung is described. Histologically-intact human A549 adenocarcinoma lung tumors were transplanted to the left lung of nude mice via a thoracotomy procedure we have developed. The transplanted tumors grew extensively locally and metastasized to the opposite lung, lymph nodes and other clinically-relevant sites. The results described indicate the model developed could have clinical relevance and contrast with models of the A549 lung adenocarcinoma constructed orthotopically with injections of cell suspensions which result in low metastatic potential.