The onset of thrombocytopenia and related factors was analyzed in patients with multiple myeloma (MM) who were receiving lenalidomide (Len) therapy at the Department of Hematology, Gifu Municipal Hospital between July 2010 and March 2014. We included 28 MM patients (18 males and 10 females) with a median age of 70.5 (range: 55-84) years. The patients were examined from the start of Len therapy until treatment discontinuation, prolongation, or dose reduction. A significant correlation was observed between platelet (Plt) count prior to the start of Len therapy (pre-treatment Plt) and the difference between pre-treatment Plt and the minimum Plt up to the point in time of treatment discontinuation, prolongation, or dosage reduction (min-Plt) (r=0.674, p<0.001). Univariate analysis revealed that factors causing thrombocytopenia of grade 2or above as a side-effect showed a significant difference when the Plt count was below the lower limit of the normal value (<14.0×10(4)/µL)(p=0.011). Factors with p<0.25 in the univariate analysis and daily dosage of Len were examined by multivariate analysis; thus, a Plt count below the lower limit of the normal value was identified as a factor (odds ratio: 15.12, 95% confidence interval [CI]: 1.712-133.5, p=0.015). In conclusion, we suggest that a Plt count below the lower limit of the normal value prior to the start of Len therapy is a prognostic factor for thrombocytopenia as a side-effect of Len therapy.