Objectives: We investigated the otolaryngological manifestations and genetic characteristics of lipoid proteinosis (LP). Methods: Twenty-two cases of LP were included. Multisystem manifestations, pharyngolaryngeal behaviors, and histopathologic and genetic characteristics were evaluated. Results: All patients presented with hoarseness as the first sign. The onset was in the newborn period in 14 cases. Video-laryngoscopy revealed irregularities along the edges and the surface of the vocal folds with diffuse yellowish deposits. In 18 cases, the oral and pharyngeal mucosa showed yellow-white infiltrates. In all cases, whitish moniliform papules were observed on the upper eyelids. In 18 cases, pocklike scars were present on the face and limbs. Histologically, there were diffuse depositions of hyaline material in the submucosa and dermis that were positive on periodic acid Schiff staining and negative on Congo red staining. Two patients had homozygous mutations in ECM1 exon 6 and exon 8, and 13 patients had heterozygous mutations in ECM1 exons. Nine patients underwent microlaryngosurgery for excision of deposits in the vocal folds. The voice function was significantly improved after operation. Conclusions: Persistent hoarseness from early infancy with laryngeal involvement is the most common feature of LP. Histopathologic characteristics and skin and mucosa changes aid in the diagnosis. Microlaryngosurgery may improve the voice function. Compound heterozygote mutations may be frequent in LP in nonconsanguineous Chinese families.