Our study concluded that statistically significant differences exist between metastatic RCC and LCC in terms of age at diagnosis, gender predilection, presenting symptoms, histo-pathology and differentiation, sites of metastases, KRAS status, and response to first-line treatment with chemotherapy plus anti-EGFR therapy. Our study is compatible with the results of most of the recent international studies and now there is a global trend for considering RCC and LCC as a two separate diseases. Further research should be done worldwide for more evaluation of the differences between RCC and LCC especially as regards molecular phenotyping and the response to targeted therapy and immunotherapy.