Objective: The Malta-UK cross-border health care collaboration gives Maltese patients access to highly specialized care that is not available locally. Our aim was to identify the issues that arise in cross-border specialized care for rare childhood diseases. Methods: We conducted 31 semi-structured face-to-face interviews with policy makers, consultant pediatricians from Mater Dei Hospital in Malta, the Royal Marsden Hospital and Great Ormond Street Hospital in England and the parents of a random sample of children referred for treatment abroad in 2011. We conducted qualitative thematic analysis of the data. Results: Respondents viewed the collaboration as successful in providing timely access to high quality specialist care. Four factors facilitated implementation: long established personal relationships; communication and data sharing; shared care approach; and well established support systems. The key challenges are logistical, financial, communication and cultural and psychological. Conclusion: Cross-border care pathways can successfully support access to high quality specialized care that is acceptable to health professionals and patients.