Background: After resection, specimens are subjected to formalin fixation during histological processing. This procedure can result in tissue shrinkage, with the amount of shrinkage related to tissue composition and tissue type.Aims: To evaluate the shrinkage of nasal mucosa and cartilage tissue and compare differences in shrinkage after resection, after formalin fixation, and during microscopic examination to understand differences in the rate of shrinkage of different tissue types. Study Design: Animal experimentation.Methods: Fresh nasal septa were excised from sheep (10 mm diameter in 40 sheep and 20 mm diameter in 40 sheep). The mucosa was separated from one side of the cartilage, with the contralateral mucosa remaining attached to the cartilage. Specimen diameters were measured in situ, after resection, after fixation for 6 or 24 hours (10% formalin), and during microscopic examination.Results: There were no differences between the in situ and after resection diameters of any tissue components (free mucosa, mucosa attached to cartilage, and cartilage) of all nasal specimens (10- or 20-mm diameter and 6- or 24-hour fixation). However, significant shrinkage occurred between resection and after-fixation. Regarding tissue specimens that were fixed for different durations (6 or 24 hours), we observed a significantly smaller mean tissue diameter in specimens fixed for 24 hours versus those fixed for 6 hours for mucosa attached to cartilage (in the 10-mm diameter after-fixation samples), free mucosa (in the 20-mm diameter after-fixation samples), mucosa attached to cartilage (in the 20-mm diameter after-fixation and microscopic measurement samples), and cartilage (in the 20-mm diameter after-fixation samples). Tissue shrinkage was greatest in free mucosal tissue and least in cartilage.Conclusion: These results should be considered when evaluating patients undergoing surgical procedures for nasal cavity and paranasal sinus malignancies. Surgical margins should be measured before fixation or evaluated if possible before fixation and shrinkage.