Sponges (Porifera) demonstrate prominent regeneration abilities and possess a wide variety of mechanisms, used during this process. In the current study, we combined in vivo observations with histological, immunohistochemical, and ultrastructural technics to elucidate the fine cellular mechanisms of the regeneration in the calcareous sponge Leucosolenia cf. variabilis. The regeneration of Leucosolenia cf. variabilis ends within 4–6 days. The crucial step of the process is the formation of the transient regenerative membrane, formed by the epithelial morphogenesis—spreading of the intact exopinacoderm and choanoderm. The spreading of the choanoderm is accompanied by the transdifferentiation of the choanocytes. The regenerative membrane develops without any contribution of the mesohyl cells. Subsequently, the membrane gradually transforms into the body wall. The cell proliferation is neither affected nor contributes to the regeneration at any stage. Thus, Leucosolenia cf. variabilis regeneration relies on the remodeling of the intact tissues through the epithelial morphogenesis, accompanied by the transdifferentiation of some differentiated cell types, which makes it similar to the regeneration in homoscleromorphs and eumetazoans.