Mucin-domain glycoproteins are densely O-glycosylated and play key roles in a host of biological functions. However, their dense O-glycosylation remains enigmatic both in glycoproteomic landscape and structural dynamics, primarily due to the challenges associated with studying mucin domains. Here, we present advances in the mass spectrometric analysis of mucins, including the characterization of mucinases, software comparisons, and complete mucinomic mapping of translationally relevant mucin proteins.