Discoidin domain receptor 2 (DDR2) is an atypical receptor tyrosine kinase that binds to and is activated by collagen in the extracellular matrix. Recent exon sequencing studies have identified DDR2 to be mutated with a 3% to 4% incidence in squamous cell cancers of the lung. This article summarizes the current state of knowledge of DDR2 biology and signaling in lung squamous cell cancer. It also explores the context-dependent role of this receptor as both an oncogene and a tumor suppressor in cancer cells. Promising therapeutic opportunities based on existing and novel targeted small molecule inhibitors against DDR2 may provide new strategies for treating lung squamous cell cancer patients.