Acute invasive fungal sinusitis (AIFS) is a fungal infection of the nasal cavity and paranasal sinuses with associated invasion of adjacent vessels and soft/hard tissues. It usually occurs in immunocompromised patients and may follow a rapid course of less than four weeks with high mortality rate. We report a 39-year-old male with relapse of acute myelogenous leukemia (AML) who was under evaluation for neutropenic fever. On his sinus CT, there was loss of calcification of his nasal septum when compared to a prior head CT, a sign indicative of an aggressive infectious process. He was diagnosed with AIFS and underwent emergent surgical debridement and systemic antifungal therapy, leading to a positive outcome. The sign described on CT (“Vanishing Nasal Septum” sign) may provide an additional, reliable tool to prospectively identify locally aggressive cases of invasive fungal infections of the nasal cavity at an earlier stage and improve patient outcomes.