Building on foundational work in activity theory and cultural psychology, this article examines children’s play to discern how biomedical practices and understandings of illness are negotiated, modeled, and reproduced among children dealing with a parent’s cancer. Using discourse analytic methods, I analyze a videotaped playroom interaction involving three preschool-age girls, all of whom have a parent with cancer, and myself. The article employs notions of `frame’ and `footing’ (Bateson, 1972; Goffman, 1974) to illustrate fantasy and reality as overlapping and embedded frames of experience that organize children’s playroom activities in distinctive ways. The shifting alignments and participation structures within the playroom environment illuminate the strategic ways in which children laminate personal experience onto the play frame. Through attention to children’s talk and embodied action, I show how children key different interactional frames to expand the realm of epistemological and cognitive resources available to them as they seek cultural understanding.