The purpose of this study was to develop a dynamic tunable focal distance graded-refractive-index lens rod-based high-speed 3-D swept-source (SS) optical coherence tomography (OCT) endoscopic system and demonstrate real-time in vivo, high-resolution (10-microm) imaging of pleural-based malignancies in an animal model. The GRIN lens-based 3-D SS OCT system, which images at 39 fps with 512 A-lines per frame, was able to capture images of and detect abnormalities during thoracoscopy in the thoracic cavity, including the pleura, chest wall, pericardium, and the lungs. The abnormalities were confirmed by histological evaluation and compared to OCT findings. The dynamic tunable focal distance range and rapid speed of the probe and SS prototype OCT system enabled this first-reported application of in vivo 3-D thoracoscopic imaging of pleural-based malignancies. The imaging probe of the system was found to be easily adaptable to various sites within the thoracic cavity and can be readily adapted to other sites, including rigid airway endoscopic examinations.