This paper presents a novel isolator that employs a varactor that tunes the operating frequency for use in future multi-band mobile handsets. The proposed isolator employs only one varactor for compactness and has a three-fold symmetric structure to reduce the parasitic reactance at each port. Analytical and experimental results clarify the tuning range of the proposed isolator. This paper presents the fundamental characteristics of the proposed isolator such as the insertion loss, isolation, and adjacent channel leakage ratio (ACLR) using a W-CDMA signal. The impact of the proposed isolator on the system performance is described based on experimental evaluation of the ACLR with a multi-band transmission system consisting of a power amplifier and the proposed isolator.