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This perspective paper introduces a new approach to assess food safety risks in circular food systems, focusing on unexpected hazards in by-products. The framework involves five key questions derived from HACCP principles, targeting risk assessment and the development of monitoring strategies. Case studies reveal the potential for hazard accumulation in circular systems and emphasize the need for ongoing research on unknown contaminants. This approach supports the European Union’s goals of sustainable, circular food systems by prioritizing food safety alongside environmental benefits.