The Tamaulipan rock rattlesnake (Crotalus lepidus morulus) is a small, cold-tolerant, mountain rattlesnake that occupies the Sierra Madre Oriental in southwestern Tamaulipas, central Nuevo Leon, and southeastern Coahuila in Mexico. The aim of the present study was to analyze and compare the protein profile and proteolytic activity of 16 individual and four pooled (representative of four regions Galeana, Santiago, Zaragoza, and Tamaulipas) venom samples of C. l. morulus from snakes collected in the northeast of Mexico. Individual and pooled venoms of C. l. morulus were analyzed by SDS-PAGE, gelatinolytic, and fibrinogenolytic assays. Additionally, the four pooled venoms were tested by 2-D electrophoresis and caseinolytic and hemorrhagic assays. Individually, venoms of C. l. morulus showed variation in their electrophoretic profile and proteolytic activity without an evident geographic trend. When comparing the pooled samples, venom from the south portion of the range (Zaragoza and Tamaulipas) showed higher proteolytic activity than samples from the central and north portion of the range (Galeana and Santiago, respectively). Furthermore, pooled venoms of C. l. morulus showed lower variation in electrophoretic profile than individual venoms. It is important to note that this is the first report of protein profile and enzymatic activities of venom of C. l. morulus.