This study integrates social network and content analyses to examine the communication behaviors of opinion leaders—such as creating threads and engaging in continuous conversations—in two large cancer-focused online health communities. Guided by the diffusion of innovation theory and the social support literature, we analyzed 951 threads and 10,179 posts and found that a group of opinion leaders (including cancer patients, family caregivers, and cancer survivors) centralized the communities from 2017 to 2018. Opinion leaders’ typical replies to others tended to be a combination of opinion support, emotional support, and network support. Amid their self-created threads, we further identified four themes: cancer history and treatment, health or life condition update, advocacy, and emotional ventilation. Implications for network and content analytics of online cancer communication are discussed.