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Communicating the diagnosis of cancer in cross-cultural clinical settings is a complex task. This qualitative research article describes the content and process of informing Zulu patients in South Africa of the diagnosis of cancer, using osteosarcoma as the index diagnosis. We used a descriptive research design with census sampling and focus group interviews. We used an iterative thematic data analysis process and Guba's model of trustworthiness to ensure scientific rigor. Our results reinforced the use of well-accepted strategies for communicating the diagnosis of cancer. In addition, new strategies emerged which may be useful in other cross-cultural settings. These strategies included using the stages of cancer to explain the disease and its progression and instilling hope using a multidisciplinary team care model. We identified several patients, professionals, and organizational factors that complicate cross-cultural communication. We conclude by recommending the development of protocols for communication in these cross-cultural clinical settings.