A paper published in the European Journal of Human Genetics addressed a conundrum that is prevalent while collecting data for rare disease research. Here the authors recognize the importance of de-identification of the samples to protect the confidentiality of the participants. However, they recognize the ethical conundrum that researchers are often faced with the re-identification of these samples, which is sometimes necessary to perform rare disease research. The authors discuss the pros and cons of de-identification and re-identification of samples. They also provide alternatives and solutions for de-identification such as open and transparent information and consent processes, using encrypted identifiers.