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Purpose: International and national research regarding the discussion of cancer treatment across cultural boundaries is sparse. This study was conducted in the province of KwaZulu-Natal, South Africa, where healthcare encounters are largely culturally discordant; and this study focused on adult Zulu patients diagnosed with osteosarcoma. The purpose of this research study was to identify the cultural factors associated with discussing the different treatment options – and to explore healthcare professionals’ responses to these cultural factors – from the healthcare professionals’ perspective. Methods: A qualitative, exploratory, descriptive and contextual research design was used. We conducted focus group interviews with professional nurses, allied health professionals and orthopaedic physicians. These three focus groups comprised a total of 23 participants, and interviews were conducted with each of these groups. We thematically analysed the interview transcripts, using Guba’s model of trustworthiness to ensure rigour. Results: We found that the factors, influencing treatment discussions in this cross-cultural clinical setting, included the meaning and the disclosure of cultural health beliefs. We identified strategies for responding to the cultural factors associated with amputation, namely timing treatment discussions, using support services, patient models and DVDs or videos. Strategies for responding to cultural and health beliefs that affect the treatment included initiating the cultural discussion, demonstrating an understanding of patients’ cultural beliefs and liaising with family and cultural decision-makers wherever possible. Conclusion: Our findings emphasised healthcare professionals’ reports of how patients can experience the discussion of culturally discordant treatment options as bad news. We recommend that the treatment discussion form an integral part of the guidelines for culturally competent communication with such cancer patients.