Self-employed individuals with cancer face unique challenges that have not been fully explored in previous research. For example, while some studies conducted in Europe have suggested that self-employed workers with cancer experience more adverse health and work-related outcomes compared to salaried workers, the specific manners in which cancer affects the health, work, and businesses of self-employed individuals remain inadequately understood. This lack of understanding represents a crucial gap in the literature, as self-employed individuals make up a significant portion of the workforce in many countries, including Canada. To address this gap, a qualitative interpretive description study was undertaken to explore the experiences of 23 self-employed Canadians diagnosed with cancer from six provinces, with the aim of generating insights into the unique challenges faced by this population. The interviews were conducted in the language chosen by the participants from the two official languages of Canada, namely English and French. Using reflexive thematic analysis, four major themes and twelve subthemes were generated from the participants’ shared accounts that reflected the impact of cancer on self-employed Canadians’ physical, cognitive, and psychological function, affecting their work ability and their ability to maintain their business and financial well-being. Participants in the study also shared strategies they used to continue working and maintain their business during their cancer experience. This study sheds light on the impact of cancer on self-employed individuals and provides insight into the experiences of self-employed individuals with cancer that can inform the development of interventions to support this population.