Background <p>Effective implementation of evidence-based programmes in real-world settings requires the capacity to adapt programmes and tailor implementation strategies to local contexts. Many primary cancer prevention (PCP) programmes that are effective in controlled settings struggle in routine practice. Although several frameworks outline principles of adaptation and tailoring, practical guidance on how to operationalise these processes remains limited. The PIECES project aims to help address this gap by developing, implementing, and evaluating structured support for tailored implementation of PCP programmes. Within the PIECES project, a toolkit was co-developed with practitioners and researchers to provide theory- and evidence-informed guidance for adapting, tailoring, implementing, and evaluating PCP programmes. The toolkit aims to strengthen implementation competencies through structured planning, collaborative learning, and evidence-informed decision-making. This paper presents the protocol for the PIECES study which evaluates the toolkit’s usability, feasibility, and mechanisms of impact of PCP programmes across diverse healthcare and community settings.</p> Methods <p>The PIECES study uses a multi-site pre-post comparative case study design with a mixed-methods implementation evaluation across 11 sites in Europe and Australia, reflecting variation in organisational structures, resources, and cultural contexts. The primary outcome is change in implementation competencies among toolkit users. Guided by the UK MRC Process Evaluation Framework and Proctor’s implementation outcomes, the process evaluation examines toolkit usability, feasibility, user satisfaction, and perceived impact on implementation processes and outcomes. Quantitative and qualitative data, toolkit log data, and structured field notes will be collected at six-month intervals (2025–2027). In parallel, a realist evaluation will explore how, why, and under what conditions the toolkit supports tailored implementation. Together, these approaches provide complementary descriptive and explanatory insights into the mechanisms and contextual factors shaping tailored implementation of PCP programmes.</p> Discussion <p>This study is expected to contribute to implementation science by evaluating a structured, evidence-informed tool designed to strengthen capacity for tailored implementation of PCP programmes. Its multi-country design offers a natural field-laboratory to explore how implementation support tools function across varying contexts. By integrating process and realist evaluation approaches, the study is designed to generate practical and theoretical evidence to inform scalable, context-sensitive strategies and enhance the sustainability and impact of evidence-based prevention efforts.</p> Trial registration <p>ClinicalTrials.gov ID NCT06718322.</p>