BACKGROUND AND PURPOSE: Many studies have observed atrophy and abnormal diffusion within the CC in MS. However, few studies have addressed whether such abnormalities appear at the earliest stage of MS, especially in CIS. In this study, we aimed to investigate the CC integrity and patterns of CC abnormalities in CIS with diffusion tensor group tractography. MATERIALS AND METHODS: First, probability maps of the entire CC and its subregions (genu, body, and splenium) were created from 19 healthy subjects. Then these probability maps were used to evaluate diffusion within the entire CC and its segments in 19 patients with CIS. Five indices, including the midsagittal CC area, FA, MD, lambda(1), and lambda(23), were used to characterize CC integrity. RESULTS: Significant differences were found between patients with CIS and healthy controls in the entire CC and its segments. For the entire CC, patients with CIS had a significantly lower midsagittal CC area and FA, higher MD and lambda(23), with a trend toward higher lambda(1). These 4 diffusion measures were correlated with T2 lesion volume. Moreover, abnormal white matter integrity was present in subregions of the CC; there was a robust significant increase in lambda(23) in the body and splenium and no difference in lambda(1) in the genu. CONCLUSIONS: Our results suggest that atrophy and abnormal diffusion inside the CC appear at the stage of CIS and the severity of damage in the genu is milder than that in the body and splenium.