PURPOSE Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Social media platforms such as Twitter are extensively used to communicate about cancer care, yet little is known about the role of these online platforms in promoting early detection or sharing the lived experiences of patients with CRC. This study tracked Twitter discussions about CRC and characterized participating users to better understand public communication and perceptions of CRC during the COVID-19 pandemic. METHODS Tweets containing references to CRC were collected from January 2020 to April 2021 using Twitter's Application Programming Interface. Account metadata was used to predict user demographic information and classify users as either organizations, individuals, clinicians, or influencers. We compared the number of impressions across users and analyzed the content of tweets using natural language processing models to identify prominent topics of discussion. RESULTS There were 72,229 unique CRC-related tweets by 31,170 users. Most users were male (66%) and older than 40 years (57%). Individuals accounted for most users (44%); organizations (35%); clinicians (19%); and influencers (2%). Influencers made the most median impressions (35,853). Organizations made the most overall impressions (1,067,189,613). Tweets contained the following topics: bereavement (20%), appeals for early detection (20%), research (17%), National Colorectal Cancer Awareness Month (15%), screening access (14%), and risk factors (14%). CONCLUSION Discussions about CRC largely focused on bereavement and early detection. Online coverage of National Colorectal Cancer Awareness Month and personal experiences with CRC effectively stimulated goal-oriented tweets about early detection. Our findings suggest that although Twitter is commonly used for communicating about CRC, partnering with influencers may be an effective strategy for improving communication of future public health recommendations related to CRC.