Sam Hopkins was born on March 15, 1912 in Centerville, Texas. In 1920, at the age of eight, Hopkins met and played with the legendary Blind Lemon Jefferson, even becoming Jefferson's guide for a short time. Hopkins' cousin, the great bluesman, Texas Alexander, was another influence. Their musical partnership was broken up by Hopkins' time in Houston's County Prison Farm during the 1930s. When Hopkins made his way to Houston's Third Ward in 1946 he was introduced to Lola Anne Cullum, a talent scout who had pieced together deals with companies such as Aladdin Records out of Los Angeles.

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