Abstract Summary In this article, we present tagtango, an innovative R package and web application designed for robust and intuitive comparison of single-cell clusters and annotations. It offers an interactive platform that simplifies the exploration of differences and similarities among different clustering and annotation methods. Leveraging single-cell data analysis and different visualizations, it allows researchers to dissect the underlying biological differences across groups. tagtango is a user-friendly application that is portable and works seamlessly across multiple operating systems. Availability and implementation tagtango is freely available at https://github.com/bernibra/tagtango as an R package as well as an online web service at https://tagtango.unil.ch.