In a method of manufacturing a complementary metal-oxide semiconductor (CMOS) image sensor (CIS), an epitaxial layer may be formed on a first substrate including a chip area and a scribe lane area. A first impurity layer may be formed adjacent to the first substrate by implanting first impurities into the epitaxial layer. A photodiode may be formed in the epitaxial layer on the chip area. A circuit element electrically connected to the photodiode may be formed on the epitaxial layer. A protective layer protecting the circuit element may be formed on the epitaxial layer. A second substrate may be attached onto the protective layer. The first substrate may be removed to expose the epitaxial layer. A color filter layer may be formed on the exposed epitaxial layer using the first impurity layer as an alignment key. A microlens may be formed over the color filter layer.