INTRODUCTION Diagnostic difficulty is frequent in primary care, yet little is known about which clinical scenarios present uncertainty to primary care practitioners (PCPs) and how they respond. We describe types of clinical scenarios causing uncertainty that PCPs brought to regularly scheduled, confidential practice meetings. Information about these patients’ characteristics and how clinicians responded could better define diagnostic uncertainty in primary care, explain and acknowledge the value of PCPs’ uncertainty work, and promote deliberate attention to its management. METHODS We analyzed case log data from 459 case scenarios where PCPs presented patients involving uncertainty to peers in “Practice Inquiry (PI) Colleague Group” meetings held in 17 San Francisco-Bay Area primary care practices between 2002–2015. Case log data included: 1) uncertainty statement/question; 2) patient and clinician information provided by PCP during first 2-3 minutes of presentation (e,g,, presenting symptoms), 3) colleagues’ responses to presentation; and 4) patient follow-up offered by presenter at subsequent meetings. Using published criteria and ones designed to identify less-objectively presented diagnostic quandaries, diagnostic uncertainty cases were selected from the larger cohort and coded to describe patients’ current status, already- known diagnoses/conditions; and diagnoses/conditions identified by presenter as possible uncertainty explanations. RESULTS Of 459 patients that PCPs presented in PI meetings, 258 (56%) involved diagnostic uncertainty. Patients’ already-known diagnoses were discussed in 72%; 44% had at least two diseases/conditions. In 52%, clinicians discussed possible diagnoses that could explain uncertainty. For these, mental health/ behavioral/ neurodevelopmental conditions were discussed as potential uncertainty contributors for approximately 25% of patients. Both diagnostic and management dilemmas were presented in 30%; diagnostic adverse events were discussed in 14% including 6 deaths. DISCUSSION PI Colleague Groups are a useful forum where clinicians can admit to being ‘stuck’ and ask for help. Certain clinical scenarios, such as patients with mental health, behavioral/neurodevelopmental conditions, presenting with new complaints, pose special diagnostic challenges. This small-group process also facilitates discussions of diagnostic error and patient harm. Further qualitative analysis of the dataset should focus on case presenters’ specific diagnostic questions, colleagues’ responses to cases presented, and how patient follow-up reported at subsequent meetings contributes to uncertainty resolution.