We conducted this retrospective study to evaluate the relationship between symptoms, histological findings, and treatment of collagenous (CC) and lymphocytic colitis (LC). We identified 19 CC and 12 LC patients having multiple colonoscopic procedures with colonic biopsies during their course of illness. A detailed histological review of all biopsies was performed. Clinical history, including symptoms and medications, was obtained in 25 of the 31 patients and was correlated with their histological findings. In all, 25% of the CC patients and 50% of the LC patients who had biopsies prior to their definitive diagnosis had the pathognomonic histological features on their prior biopsies to some extent (but were not recognized by the pathologists); however, these features were more pronounced on the biopsies from the procedure that established the diagnosis. Nonetheless, 10 of 12 such patients with clinical data available had symptoms and were being treated at the time of prior biopsies. Assessment of the relationship among histological, clinical and therapeutic data showed no association between symptoms or histological findings and treatment with any medication. In summary, in this sample of CC and LC patients, symptoms often precede fully developed histological features. No change in symptoms or histological findings was found to be associated with medication.