Despite the worldwide vaccination, the COVID-19 pandemic continues as SARS-CoV-2 evolves into numerous variants. Since the first identification of the novel SARS-CoV-2 variant of concern (VOC) Omicron on November 24th, 2021, from an immunocompromised patient in South Africa, the variant has overtaken Delta as the predominant lineage in South Africa and has quickly spread to over 40 countries. Here, we provide an initial molecular characterization of the Omicron variant through analyzing a large number of mutations, especially in the spike protein receptor-binding domain with their potential effects on viral infectivity and host immunity. Our analysis indicates that the Omicron variant has two subclades and may evolve from clade 20B instead of the currently dominant Delta variant. In addition, we have also identified mutations that may affect the ACE2 receptor and/or antibody bindings. Our study has raised additional questions on the evolution, transmission, virulence, and immune escape properties of this new Omicron variant.