Cambarus (Puncticambarus) smilax is a stream-dwelling crayfish that appears to be endemic to the Greenbrier River basin in the Valley and Ridge province of West Virginia. Within the Greenbrier system it occurs primarily in tributaries to the Greenbrier mainstem, with stable populations in the East and West Fork, and Thorny, Knapp, and Deer creeks. The new species is morphologically most similar to C. (P.) robustus, from which it can be distinguished by a combination of the following characters: adult palm length comprising 73–76% of palm width as opposed to 63–70% in C. (P.) robustus; ventral surface of chela of cheliped with 0–2 subpalmar tubercles compared to 3–6 subpalmar tubercles in C. (P.) robustus; lack of tubercles on the dorsal surface of chela; longer, more tapering, less rectangular rostrum (47–52% rostrum width/length ratio) compared to C. (P.) robustus shorter, less tapering rectangular rostrum (54–63% rostrum width/length ratio); and the central projection of the form-I male gonopod curved ≤90 degrees to the shaft.